Conventional examples of methods for producing chromane compounds include a multi-step method in which a phenol and an unsaturated carbonyl compound are used as starting materials (see, for example, Patent Document 1); and a method in which a phenol, a formaldehyde, and an unsaturated compound are allowed to react without use of any catalyst or in the presence of an acid or amine (see, for example, Patent Documents 2, 3 and 4).
An optically active 6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid derivatives can be obtained by way of an optical resolution of 6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid ester obtained by the method of Patent Document 4, in accordance with 1) a diastereomeric resolution with an optically active amine (see, for example, Patent Documents 5 and 6); or 2) an enantiospecific hydrolysis of (±)-6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid ester using an enzymatic catalyst (see, for example, Patent Document 7).
Although it is possible to produce S-(−)-6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid in accordance with the above mentioned methods, there are still some points which require improvement when high purity S-(−)-6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid is provided industrially and economically. The present inventors have already proposed methods for producing 6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid easily in good yield. However, even in these methods, when S-(−)-6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid ester is produced and then hydrolyzed to produce S-(−)-6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid, the resulting S-(−)-6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid is deteriorated in yield and purity, producing a reacted solution in the form of a pasty inseparable slurry, if operation conditions after the hydrolysis are improper.
Therefore, for the practice on an industrial scale, it is required to establish means for solving these problems to obtain the target product economically. However, none of the conventional and prior art references has disclosed a production condition for S-(−)-6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid excellent in efficiency such that solid/liquid separation and drying of crystals are made easier.    Patent Document 1: U.S. Pat. No. 4,026,907 specification    Patent Document 2: Japanese Patent Laid-Open (Kokai) No. S60-92283    Patent Document 3: Japanese Patent Laid-Open (Kokai) No. H7-97380    Patent Document 4: Japanese Patent Laid-Open (Kokai) No. 2003-146981    Patent Document 5: Japanese Patent Laid-Open (Kokai) No. H11-80149    Patent Document 6: International Publication No. WO02/12221 pamphlet    Patent Document 7: U.S. Pat. No. 5,348,973 specification